|Year : 2023 | Volume
| Issue : 1 | Page : 4-12
Pragmatic and early usage of statin in patients with diabetes for prevention of atherosclerotic cardiovascular disease: Survey-based opinions of indian health-care practitioners
Sanjay Kalra1, Surender Kumar2, Kaushik Pandit3, R Anantharaman4, Atul Dhingra5, I Periyandavar6, Manoj Chawla7, Mohan Magdum8, Piyush Desai9, Prasun Deb10, Senthil Kumar Rajasekaran11, Ramesh N Nair12, Shehla Shaikh13, Subodh Banzal14, Sunil Kota15, Tejas Shah16, Santosh Y Revankar17, Amit Gupta17
1 Department of Endocrinology, Bharti Hospital, Karnal, Haryana, India
2 Department of Endocrinology, Ganga Ram Hospital, New Delhi, India
3 Department of Endocrinology, Fortis Hospital, Kolkata, West Bengal, India
4 Magna Clinics for Obesity Diabetes and Endocrinology, Bengaluru, Karnataka, India
5 Department of Endocrinology, Gangaram Bansal Hospital, Sri Ganganagar, Rajasthan, India
6 Saroja Diabetic Centre, Chennai, Tamil Nadu, India
7 Lina Diabetes Centre, Mumbai, Maharashtra, India
8 Poona Hospital and Research Centre, Pune, Maharashtra, India
9 Advanced Diabetes Centre, Surat, Gujarat, India
10 Department of Endocrinology, KIMS Hospital, Hyderabad, Telangana, India
11 Department of Endocrinology, PSG Hospitals, Coimbatore, Tamil Nadu, India
12 Department of Endocrinology, Bharath Hospital, Kottayam, Kerala, India
13 KGN Diabetes and Endocrine Centre, Mumbai, Maharashtra, India
14 Obesity Thyroid and Hormone Research Center and Gyane Clinic, Indore, Madhya Pradesh, India
15 Diabetes and Endocare Clinic, Brahmapur, Odisha, India
16 IVA Speciality Clinic and Diabetes Care Centre, Mumbai, Maharashtra, India
17 Medical Services, USV Private Limited, Mumbai, Maharashtra, India
|Date of Submission||14-Oct-2022|
|Date of Decision||30-Sep-2022|
|Date of Web Publication||18-Jan-2023|
Santosh Y Revankar
USV Private Limited, Mumbai, Maharashtra
Source of Support: This project has been funded by USV Pvt. Ltd, Conflict of Interest: Dr. Santosh Revankar and Dr. Amit Gupta are employees of USV Pvt Ltd. All other authors have no conflicts of interest to declare
Background: An early initiation of statins in the diabetes population helps in prevention of atherosclerotic cardiovascular disease (ASCVD). However, there is a paucity of data on its use in young Indian patients with diabetes. This survey report aimed to provide opinion-based recommendations for pragmatic usage of statin in diabetes population of India. Material and Methods: Discussion and virtual survey (a questionnaire of 18 questions) was conducted at 16 round table meetings (RTMs) which included participation of health-care practitioners (HCPs) from India. On the basis of their opinions and discussion, general recommendations about early usage of statins in diabetes for prevention of ASCVD were derived. Results: Out of 261 HCPs participated, 56.1% recommended initiating statins in patients aged 41–50 years irrespective of their total/low-density lipoprotein cholesterol (LDL-C) levels. Among people with diabetes aged between 20 and 39 years, 38.9% of HCPs considered LDL-C >100 mg/dL and 77% of HCPs considered history of ASCVD as a risk factor for early statin initiation. Overall, 98.9% of HCPs agreed that early initiation of statin in people with diabetes and ASCVD risk factors will help reduce ASCVD. The majority of HCPs recommended initiating moderate-intensity (51.2%) and low-intensity (43.8%) statins and assess every 3 months for tolerance and compliance in people with diabetes (aged 20–39 years) and additional ASCVD risk factors. The use of rosuvastatin (78.5% of HCPs) was preferred for early initiation in people with diabetes. Majority of HCPs agreed (57.3%) or strongly agreed (36.2%) that rosuvastatin has more clinical utility compared to other statins due to better LDL-C-lowering effect and other pleiotropic effects. Physician's inertia limits the effective use of statins among young adults with diabetes (55.8%), and 65.8% of HCPs recommended screening of people with diabetes for additional ASCVD risk factors. Conclusion: The participating HCPs opined that early initiation of statin therapy in people with diabetes and ASCVD risk factors will help reduce ASCVD. Rosuvastatin is mostly recommended for early initiation of statin therapy among the diabetes population for prevention of ASCVD. There is a necessity of using a proactive approach to screen for additional ASCVD risk factors in young individuals with diabetes and further increase the awareness about benefits of initiating statin therapy from an early stage.
Keywords: Atherosclerotic cardiovascular disease risk factors, health-care practitioners, low-density lipoprotein cholesterol, recommendations, rosuvastatin, virtual survey
|How to cite this article:|
Kalra S, Kumar S, Pandit K, Anantharaman R, Dhingra A, Periyandavar I, Chawla M, Magdum M, Desai P, Deb P, Rajasekaran SK, Nair RN, Shaikh S, Banzal S, Kota S, Shah T, Revankar SY, Gupta A. Pragmatic and early usage of statin in patients with diabetes for prevention of atherosclerotic cardiovascular disease: Survey-based opinions of indian health-care practitioners. Chron Diabetes Res Pract 2023;2:4-12
|How to cite this URL:|
Kalra S, Kumar S, Pandit K, Anantharaman R, Dhingra A, Periyandavar I, Chawla M, Magdum M, Desai P, Deb P, Rajasekaran SK, Nair RN, Shaikh S, Banzal S, Kota S, Shah T, Revankar SY, Gupta A. Pragmatic and early usage of statin in patients with diabetes for prevention of atherosclerotic cardiovascular disease: Survey-based opinions of indian health-care practitioners. Chron Diabetes Res Pract [serial online] 2023 [cited 2023 Jun 2];2:4-12. Available from: https://cdrpj.org//text.asp?2023/2/1/4/368025
| Introduction|| |
The development of atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality; rises with age, reduces quality of life, and begins early in people with diabetes., In India, the prevalence of coronary artery disease (CAD), ischemic heart disease, stroke, and peripheral artery disease among patients with diabetes is increasing at an alarming proportion. Statins remain the first-line therapy for the management of ASCVD risk in all patients. It has been stated that the use of statins can reduce symptoms of coronary heart disease (CHD) and acute coronary events in people with type 2 diabetes mellitus (T2DM)., Statins were associated with a reduced incidence of ASCVD and mortality regardless of their low-density lipoprotein cholesterol values or history of cardiovascular disease.,
Many national and international guidelines have recommended the routine use of statins in patients with diabetes.,, According to the American Diabetes Association (ADA) guidelines, statin therapy is recommended in people with diabetes of all ages with ASCVD along with lifestyle intervention. Furthermore, these guidelines suggested the use of moderate- and high-intensity statin therapy in people with diabetes (aged 40–75 years) without ASCVD and people with diabetes (aged 50–70 years) with multiple ASCVD risk factors, respectively. An early initiation of statin therapy along with lifestyle modification should be indicated in people with diabetes aged 20–39 years with ASCVD risk factor. The Research Society for the Study of Diabetes in India-Endocrine Society of India (RSSDI-ESI) guidelines for management of diabetes advocated statin use in patients with ASCVD risk, and intensification of statin therapy should be considered according to CVD risk, age, low-density lipoprotein cholesterol (LDL-C) level, and side effects.
The use of statin was significantly associated with reduced all-cause mortality and cardiovascular (CV) risks in elderly patients. Globally, statins have been found to be effective and safe in young people with dyslipidemia and adults with diabetes in terms of preventing vascular complications and mortality., However, the statin use in the management of diabetes is very low in Indian subcontinents. A real-world study (LEADD Study) included 4002 patients with diabetes and dyslipidemia and reported that recommended statin dose is not achieved and low adherence level was observed in majority of patients associated with ASCVD risk factors and ASCVD. A clinical study reported only half of the people with diabetes prescribed with statins, and the use of higher dose is very low among these patients. In addition, it was reported that lesser number adults aged <40 years receive statin than those >40 years. A case-based questionnaire conducted with 2248 Indian patients showed that concomitant statin therapy along with glimepiride and metformin combination has shown good clinical efficacy with glycemic control and is beneficial, particularly to ensure more cardioprotection.
Despite recommendations for the use of statins at an early stage, there is a paucity of data on its use, particularly in young Indian patients with diabetes. Therefore, this survey report aimed to analyze the opinion of clinical experts on early usage of statin in people with diabetes as well as to provide opinion for early and pragmatic usage of statins in people with diabetes from India.
| Methods|| |
Standard questionnaire pertaining to the usage of statin in the diabetes population was prepared, discussed, and evaluated by experts which included participation of a diverse panel of health-care practitioners (HCPs) including diabetologists, endocrinologists, consultant physicians, and family physicians. These HCPs were from the different geographical regions of India.
All the participated HCPs were requested to take part in a survey that included a standard questionnaire of 18 questions about early usage of statin in the diabetes population of India. They were sent an introductory email containing a link of the survey, and this survey was conducted for a 2-month period from April 2022 to May 2022. The survey results were discussed during the 16 Pan India round table meetings (RTMs) between June 2022 and July 2022, and opinions from the experts were noted. On the basis of these opinions and discussion, general insights were derived and compiled to prepare this survey report on early and pragmatic usage of statins in the diabetes population of India to prevent the risk of ASCVD.
| Results|| |
A total of 261 HCPs participated in the survey and RTMs, majority of which were diabetologists (n = 185, 70.9%) followed by endocrinologists (n = 36, 13.8%), consultant physicians (n = 28, 10.7%), and family physicians (n = 12, 4.6%) [Figure 1]. A total of 98 (37.5%), 62 (23.6%), 56 (21.6%), and 45 (17.4%) HCPs were from the Southern, Western, Northern, and Eastern parts of India, respectively [Figure 1].
|Figure 1: Specialty and geographical distribution of HCPs. HCPs = Health-care professionals|
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The majority (56.1%) of HCPs mentioned that they would initiate statins in patients aged 41–50 years irrespective of their total cholesterol/LDL-C levels [Figure 2]. The Around 38.9% of HCPs considered LDL-C >100 mg/dL to initiate statin therapy in patients aged 20–39 years [Figure 2]. A total of 32.1% of HCPs opined that they would initiate statins in 16%–30% of their patients aged <40 years [Figure 2]. A total of 70.5% of HCPs agreed that they would initiate statin therapy in >40% of their patients with diabetes aged 40–75 years and not having ASCVD [Figure 2].
|Figure 2: Initiation of statin therapy. ASCVD = Atherosclerotic cardiovascular disease, LDL-C = Low-density lipoprotein cholesterol|
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Atherosclerotic cardiovascular disease risk
A total of 98.9% of HCPs agreed or strongly agreed that early initiation of statin in patients with diabetes and ASCVD risk factors will help reduce CVD risk [Figure 3].
|Figure 3: Initiation of statin therapy and ASCVD risk factor. ASCVD = Atherosclerotic cardiovascular disease, BMI = Body mass index, FH = Family history, LDL-C = Low-density lipoprotein cholesterol, WC = Waist circumference|
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A total of 90.1% of HCPs agreed or strongly agreed that every patient with diabetes in India (aged 40–75 years) with no ASCVD should be on at least moderate-intensity statin therapy for ASCVD prevention [Figure 3]. In total, 77% of HCPs considered family history of ASCVD as a risk factor for early statin initiation among 20–39 years of patients with diabetes [Figure 3].
A total of 61.9% of HCPs considered that there is a moderate risk of ASCVD in patients after the diagnosis of diabetes mellitus who have no other risk factors [Figure 3].
Opinion on treatment and outcomes
The majority of HCPs recommended to initiate moderate-intensity statins (51.2%) and low-intensity statins (43.8%) and assess every 3 months for tolerability and compliance in patients with diabetes (age group of 20–39 years) and additional ASCVD risk factors [Table 1].
A total of 78.5% of HCPs recommended the use of rosuvastatin for early initiation in patients with diabetes aged 20–39 years [Table 1]. Majority of HCPs agreed (57.3%) or strongly agreed (36.2%) that rosuvastatin has more clinical utility compared to other statins due to better LDL-C-lowering effect and other pleiotropic effects [Figure 4].
|Figure 4: Opinion on awareness of early usage of statins and CVD outcomes. CVD = Cardiovascular disease, LDL-C = Low-density lipoprotein cholesterol|
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A total of 61.5% of HCPs mentioned that they assess lipid profile after 3 months of initiation of statins in patients with diabetes. In case of patients with diabetes >40 years of age with uncontrolled lipid levels with one ASCVD risk factor or in case of patients with >2 ASCVD risk factors irrespective of lipid levels, 27.0% and 28.2% of HCPs recommended early use of high-intensity statins, respectively [Table 1]. The majority (78.1%) of HCPs considered that early initiation of statins among young adults with diabetes results in reduction of future CVD events [Figure 5].
|Figure 5: Outcome, limitation of effective use, and intervention for early statin usage in diabetes. ASCVD = Atherosclerotic cardiovascular disease|
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In addition, a total of 55.8% of HCPs considered that physician's inertia limits the effective use of statins among young adults with diabetes [Figure 5]. A majority of HCPs agreed or strongly agreed with the fact that there is a need to increase the awareness of early use of statins for primary prevention of CVD among Indian health-care professionals [Figure 4]. A total of 65.8% and 53.8% of HCPs recommended “screening of patients with diabetes for additional ASCVD risk factors” and “continuing medical education to physicians on early statin usage benefit” as the most appropriate interventions, respectively, to improve early usage of statin in patients with T2DM [Figure 5].
| Discussion|| |
It is well established that treating conventional CV risk factors which include hypertension and dyslipidemia is pivotal in all adult patients irrespective of their patients with diabetes status to improve their long-term survival.,, Indeed, myocardial infarction is the leading cause of morbidity, mortality, and re-infarction. There is a large body of evidence available in support of the use of statins to reduce ASCVD risk in patients with diabetes.,, Statin therapy has been shown to attenuate vascular inflammation and endothelial dysfunction in patients with diabetes. Recent international as well as national guidelines recommend the use of statins in individuals with diabetes for primary prevention of CV events.,,,,,, However, guidance on early initiation of statin therapy in young individuals with diabetes with or without ASCVD risk factors is lacking in Indian scenario. Therefore, the present survey report attempted to collect and present a comprehensive opinion of experts from India on early usage of statin in diabetes population of India.
The key observations of this study highlight the statin initiation approach used in current clinical practice and further emphasize on the importance of statin initiation at an early age among diabetes population of India for prevention of future risk of ASCVDs.
According to the present study, in the routine clinical practice, majority of HCPs opined that the statins are initiated in patients with diabetes aged 41–50 years irrespective of their total/LDL-C, and in case of young patients with diabetes aged between 20 and 39 years with LDL-C >100 mg/dL, an early initiation of statin therapy should be considered. However, HCPs agreed to initiate statin therapy in around one-third of diabetes population aged <40 years. ADA 2022 guidelines also support the initiation of statin therapy along with lifestyle modification in patients with diabetes aged 20–39 years with additional ASCVD risk factors. The Lipid Association of India has recommended statins for the treatment of lipid management to reduce ASCVD risk.
In the present survey, around 70% of HCPs recommend to start statin therapy in >40% of their patients with diabetes aged 40–75 years and not having ASCVD. ADA 2022 guidelines are in accordance with this recommendation wherein moderate-intensity statin therapy in combination with lifestyle modification is suggested for patients with diabetes aged 40–75 years without ASCVD. The guidelines also recommended that either high-intensity or moderate-intensity statin therapy should be used together with lifestyle intervention according to patient age and ASCVD risk factors. Similarly, RSSDI-ESI Consensus Group 2020 and European Society of Cardiology (ESC) 2019 guidelines recommend the initiation of statin therapy along with lifestyle modifications in all patients with diabetes having CVD risk, if not contraindicated, and titration of dosage strength of statins can be done based on patient's CVD risk, age, side effects, tolerability, and LDL-C levels., In the present survey, a majority of HCPs agreed that every patient with diabetes in India (aged 40–75 years) with no ASCVD should be on at least moderate dose of statin for ASCVD prevention. Therefore, this survey emphasizes on early initiation of statin therapy in the younger population of diabetes irrespective of the baseline LDL-C levels. Further, participating HCPs highlighted that the history of smoking, sudden cardiac deaths in family, and other cardiac events should be considered in the younger population while initiating statin therapy and the combination of statin and lifestyle modifications have shown to be most effective in these patients with diabetes. Generally, all patients with diabetes aged <40 years should be given the benefit of statin therapy irrespective of their age. Another opinion put forth by a cardiologist was to consider initiating statins in patients with LDL-C <80 mg/dL, and with a family history of CAD. It was pointed out that the level of LDL-C does not influence the use of statins in patients with diabetes; however, the presence of risk factors along with LDL-C >70 mg/dL is riskier than LDL-C <100 mg/dL without risk factors.
Almost all the HCPs were in agreement with the fact that early initiation of statin in patients with diabetes and ASCVD risk factors will help to reduce CVD risk. Further, it was suggested that while on statin therapy, instead of achieving the 50% LDL-C reduction goal, it is vital to focus on reducing LDL-C levels to target levels.
In the young individuals aged between 20 and 39 years with diabetes, majority of HCPs recommended to consider family history of ASCVD as a major risk factor for early statin initiation. Further, presence of hypertension, family history of microvascular diseases such as patients with diabetes kidney disease and retinopathy, presence of persistent high microalbuminuria, increased body mass index, elevated total cholesterol levels, and smoking or tobacco use should also be considered CVD risk factors and statin therapy should be initiated early in such patients.
With respect to different approaches suggested for the early usage of statin in young individuals with diabetes aged between 20 and 39 years and with additional ASCVD risk factors, majority of participating HCPs opined that initiating low- or moderate-intensity statin therapy and assessing every 3 months for tolerance and compliance is the preferred approach. Postinitiation of statin therapy, lipid profile assessment was suggested after 3 months by majority of HCPs. Further, among different statin treatment options for patients from young age group (20–39 years), rosuvastatin therapy was preferred option over other statins due to its better LDL-C-lowering effect and other pleiotropic effects. A small percent of HCPs opined for addition of ezetimibe to statin therapy. However, a study by Cannon et al. reported a benefit of the use of ezetimibe in combination with statin in terms of CVD risk reduction through LDL-C reduction among T2DM population. In addition, compared to statin therapy up-titration, this approach showed an ability of greater LDL-C reductions and target achievement among patients with CHD risk.
ADA 2022 recommends the use of high-intensity statin therapy in patients with diabetes and with multiple ASCVD risk factors or aged 50–70 years. The present survey findings are also parallel to this recommendation suggesting the use of high-intensity statin therapy for patients aged >40 years with uncontrolled lipid levels with at least 1 or >1 ASCVD risk factor or in case of patients with >2 ASCVD risk factors irrespective of lipid levels.
A majority of participating HCPs believe that an early initiation of statin therapy among young adults with diabetes results in reduction of future CVD events and major coronary events. A recent study from the US supports this notion wherein the authors showed that in young adults, lipid lowering with statins or lifestyle interventions would prevent lifetime ASCVD events. However, more than half of the participating HCPs believed that physician's inertia is the most common limiting factor for effective use of statins among young adults with diabetes. Thus, there is a need to increase the awareness of early use of statins for primary prevention of CVD among Indian health-care professionals. The most appropriate approaches suggested to tackle this challenge include screening of patients with diabetes for additional ASCVD risk factors and continuing medical education to physicians on early statin usage benefit. As per the Indian Council of Medical Research guidelines, the screening of patients with T2DM for CVD risk is an important strategy for reducing mortality and CVD events.
It is noteworthy to consider that statin use can be a contributing factor for the development of new-onset diabetes type 2 due to their link with increased insulin resistance.,,,, In spite of statins being associated with incident T2DM, the results of JUPITER trial (wherein statin treatment was beneficial in prevention of 134 vascular events or deaths for every 54 new cases of diabetes diagnosed) support a risk–benefit ratio in favor of statins. However, it is important to diagnose people at high risk of developing diabetes before initiating statin treatment.
The authors acknowledge the following limitations of this paper. First, the opinion provided in this paper is based on insights gathered from survey with smaller sample size; however, further studies with large sample size may be needed to corroborate these results. Second, an inherent limitation of the study is that these insights were not based on patients' experience and are the opinion of treating HCPs. Hence, care must be taken when generalizing these results.
| Conclusion|| |
Overall survey results indicate that early initiation of statin therapy in patients with diabetes and ASCVD risk factors will help reduce CVD risk. Rosuvastatin is mostly preferred for early initiation of statin therapy among the diabetes population for prevention of ASCVD. There is a necessity of using a proactive approach to screen for additional ASCVD risk factors in young individuals with diabetes and further increase the awareness about benefits of initiating statin therapy from an early stage.
Ethics committee approval was not obtained for this study considering this was an HCP survey and no patient data was used.
We acknowledge Ms. Farida Hussain, Ms. Anuj Maheswari, and Ms. Annsusan Renji from USV Pvt. Ltd. for their assistance in carrying out the project. The medical writing support was provided by Dr. Tejal Vedak from Sqarona Medical Communications LLP (Pune).
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]